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I Patented Jan. 20, 1931 I l a .v UNITED STATES, r nonms s. cnRswEL 0155s1 Louis, ivrrssonitn iissienoa To MoNsANTo WORKS, or $1. LOUIS,MISSOURI, n'conronnrionnor MISSOURI Rimmin that formsthe,subject-inatter of the pending I pounds.

' riaocnss uon o'iamm ne IsonueE'Non This invention relates to processesof the kindthat are used for produclng or obtaining ls'oeugenol, andparticularly, to the process application for patent of James C.Ballantyne, filedJuly 12,1926, milder-Serial No.

122,050, and entitled: Process for producing I isoeugenol andisochavibetol; I

One object of my invention is to provide a novel process for obtainlngpure lSOGUigGIlOl that issubstantially free of isomeric com Anotherobject is to provide a process by which a mixture of alkyloxyisoeugenoland alkyloxyisochavibetol can be easily separated.

The Ballantyne process described in, the

' pending application for patent above retion and hydrolysis, andthereafter, separat ferred to contemplates converting a mixturecontaining alkyloxyisoeugenol. and: alkyl-' 'oxyisochavibetol into acrystalline. mixture of isoeugenol and isochavibetol by methylaing theliquid isoeugen'ol'fro-m the crystalline 4 isochavibetol. My processalso contemplates starting with a; mixture containing alkyloxyisoeugenoland alkyloxyisochavibetol, but

instead of subjecting the said mixture to such treatment as to transformthe isomers'into soeugenol and isochavibetol'or homologues V ofisoeugenol and isochavibetohas contemplated by thesaid Ballantyneprocess, I first subject themixture to such treatmentas to;

effect the separation of" the alkyloxyisoeu genol from thealkyloxyisochavibetol, and thereafter, I separately-transform each iso-Iner into isoeu 'enol.

1 tially free of isomeric compounds;

example, by treating'safrol or isosafrol Witlr' t v The filtrate or:alcoholic l quor y VlllOlTiCOnalcohol and caustic potash in an autoclaveat J about 135 0., when the following reaction takes place:

'-oH2 ornon 7 cess of alcohol is removed, and the. product Bythisprocedure I am able to easily dbtain pure isoeugenol substan-QHzCliLOHa- -is acidified,.vvhen a mixture'is obtained which 1s composedof two' isomers having j :the following constitution:

I 0 mm, v cnzo lom and A OOHzOR salts of the isomers, and thereafter,separat-- 7 ing the calciumsalt of alkyloxyisoeugenol I from the calcium-salt of alkyloxyi-sochavibetol by filtration, centrifuging or any otherpreferred procedure, itbeing possible to read- 11y separatesaidfsalts,=due to the fact that I the calciumfsalt of alkyloxyi'soeugenol, is rel-'atively solubleinalcohol, and the other salt, i. e'., the calcium saltof alkyloxyisochavib'etol, is relativelyinsolublel, Instead of treatingthe mixed-isomers in alcoholic solution, as 7 above described, themixedisomers cal l be first converted intothe calcium salts and then.treatedvvithalcohol, so asto dissolve the calcirimTsalt of isoeugenol,and said salt thereafter removed. In either case,.the formationofthecalcium saltsis expressed by the following equations oizccnlorhonionom g Insoluble tains the soluble calcium salt of alkyloxyiso'eugenol isthen treated so-astorecover the alkyloxyisoeugenol,and the insoluble salt of alkyloxyisochavibetol is treated so asto,-re-' cover the al kyloxyisochavibetol.v V f i r One'procedure thatbe"'follovved in practising my. process-is as follows: A mixtureofjalkyloxyisoeugenol andalkyL oxyisochavibetol isobta-ined bymixingsafrol with. caustic potash and methyl-alcohohand.

fheating said mixture man autoclave." The product is poured into Water,Washed with benzol to remove isosafrol, acidified, extracted, and theextract'carefully Washedand dis- 'tilledin vacuum, thereby producin tureof methoxyisoeugenol and medioxyisochavi-betol. 300 gr. of the saidisomeric mixture of metho' xyi'so'eugenol and. niethoxyisocalcium oxide.

chavibetol are then dissolved in 1950 cu. cen. of denatured alcohol,together ivithfio grr'o'f' alcohol and said filtercake is thenacidified,

whereby a yield of 177 ofni'ethoxyisochavibetol is obtained. Thefollowing series of reactions illustrates the above processup toonzorrom ornoirom H oinoMe onzoilcr'n 01110110133 2 Houdini; O'CHiOMB011 i H CHgOMe "oirorrors on cam OOHzOMe A 0 V o, Y oHzoMe V SolubleInsoluble, Filtered-off enema, Gaze-11cm i The filtrate. resulting fromthe abovefde scribed filteringi'operationfis then diluted with 500 cu.cen. of water an'd'is traction ally distilled. so as to; remove thealcohol. The residue from the distillation is thenacidi Y The mixture isstirred for 3' hours and filtered, centrifuged or otherwise i treated toremove the insoluble salt. The filter cake is then washed with 500 cu.cen. of

CHrOHIGHi T The following series of tra'te's the operationof. this stageof the ified, whereupon a yield of 120 gr. of methoxyisoeugenol isobtained The separated ls om'ers are then convertedzlnto isoe'ug'enol 1nany suitable manner; It is immaterial what procedure is used to effectsuclrconversion,

-.lout the following-examplesex lain two dif -erent tvayso'foarryiingout this step of the process; ."The*hlStllOXYiSOChEl-VlbtOl istreated in alkaline solution with dimethyl sulfate When the f reactionis complete, the oil layer 1 is separated and dissolved in aqueousalcohol', Dilute. hydrochloric acidis added, ant-l the mixture isheated'until allot the .3116 thojxy group has [been hydrolyzed. The

acid is then neutralized and thelalciohol is re-. moved hy jfractionaldistillation. When theresidue) is cooled, isoeugenol separatesgas anoily -layer.- "The oily; layer Iis-removed-and distilled under vacuumwhen there is-obtained distillate consisting of isoeugenol, practicallypure andfree from isomers,-

The following series of reactions illustrates the operation of thisstage oi-the process; p

OHgCl-IQH: 011011.011;

5011200113 V dcmoofis A "omoHcHi 011123.011:

v diLacid OM, is alcohol 0M8 ftJHzOCHi: V I

2 The metho'xyisoeugenol is dissolved in aqueous alcohol containing alittle hydro chloric acid, and the mixture is gently heat-- ed until themethoxy group is-hydrolyzed. Vvhen this hydrolysis is complete, themixture is cooled andan excess of sodium hydroxide is added. To thismixture is then added dimethyl sulfate. When the reaction c is-complete, the resulting mixtureis fractionally distilledto remove thealcohol; .The-

residue is acidified, when an. oily layer separates, The Oil layer-1S;'16H1*0V6Cl and distilled under vacuum, when there is obtaineda furjther yield, ofxisoeugenol, practically; pure and free of isomers;

process CH:'GH.'CH3 oircrizom HaHzQ reactions il'lus;

ethyl alcohol, and to this solution isadded 0.29.1:gfof calciumhydroxide. The mixture is stirred for 3 hours and filtered, centri-Iuged or. otherwlse treated to remove. the 1n-" soluble salt. The filtercake is washed with 1.5 liters of alcohol and then sludged up with5-liters of water. (14kg. ofsoda ash and the mass is boiled for 1 hour.After cooling, the mixture is filtered or otherwise treated to removethe insoluble calcium carbonate. The filtrate of this secend filteringoperationis acidified, whereby a yield of 0.6 kg. ofmethoxyisochavibetolwill be obtained. The alcoholic filtrate of the first filteringoperation is combined with the alcohol wash liquor and diluted with twoliters of water and fractionally distilled to.

recover the alcohol. IThe distilled residue is then acidified, whereupona yield of0.3 kg. of methoxyisoeugenol is obtained.

The following series of reactions illustrate the operation of the abovedescribed process:

The separated isomers are then converted into isoeugenol, as specifiedin the first example of my process previously described.

Having thus described my invention, what I claim as new and desire tosecure by Let- -ters Patentis: l

' 1. In a process for obtaining or producing isoeugenol, theprocedureconsisting in subjecting a mixture of alkyloxyisoeugenol and.

alkyloxyisochavibetol to such treatment as to convert said mixture intothe calciumsalts of the isomers, and separating the calcium salt of'alkyloxyisoeugenol from the calcium:

salt of alkyl0xyisochavibetol;

5; 2. Inaprocess forobtaining'orprodllcing isoeugenol, theprocedurewhich consists in converting a mixture. of. alkyloxyisoeugenolr and ulkyloxyisochavibetol,in. alcoholic .s0lution into thecalcium-saltaof alkyloxyisochavir betoland the salt of alkoxyisoeugenolil ,3..I1i a roces's for,. obtainin or roducin v r bisoeugenol, 'tl efprocedure, which consists :in

converting a mixture ofimethoxyisoeugenol andlmethoxyisochavibetol inalcoholic-'solu r tion into the calcium salts of 'thei s'omers, and

V removingthe insolublefcalcium'salt ofmeth To-this mixtureis added Ioxyisochavibetol. I

V 4. A process for obtaining or producing isoeugenol, characterized byconverting a mixture of alkyloxyisoeugenol and alkyloxyisochavibetolinto the calcium salts. of the isomers, treatingthe mixed calcium saltswith alcohol so as to dissolve the soluble calcium salt of isoeugenol,and then removing the sol-' uble calcium salt of alkyloxyisoeugenol. y

5. A processfor. producingor obtaining; isoeugenol, characterized byconverting a mixture of methoxyisochavibetol andmethsoxyisoeugcnol'into'the; calciiun salts-of the isomers,- treating themixed calcium salts with alcohol so as to dissolve the soluble calciumsalt of methoxyisoeugenol, and then removing V the soluble calcium saltof methoxyisoeugee nol. i V V I 6. In a process for obtaining orproducing isoeugenol, the procedure. whichconsists in converting amixture of alkyloxyisochavibetol and alkyloxyisoeugenol in alcoholic soeI V lution into thecalciuni salts of theisomers, removing the insolublesalt of alkyloxyisochavibetol, andtreating the separated calciumis'altsin such a way as to recover the 1101 in a substantially purestate. 7

7 In a; process for .producing'orobtaining alkyloxyisochavibetol and'alkyloxyisoeugeisoeugenol, the procedure which consists in converting amixture J of methoxyisochavibef tol and methoxylsoeugenol in alcoholicso-' I lution into the calcium salts "of the isomers, by treatment'withcalcium oxide or calcium hydroxide, removing the. insoluble salt ofalkyloxyisochavibetol, and treating the separated calcium salts with anacidic body to recover" the alkyloxyisochavibetol and alkyloxyisoeugenolin a substantially pure state. 7 8. Aprocess' for separatingalkyloxyisoe;

chavibetol from .alkyloxyisoeugenol, consisting in converting amixtureof such isomers 7 into the calcium salts of the isomers, bytreatment with calcium oxide or calcium hydroxide, treating the calciumsalts with alcohol so as-to dissolve the insoluble calcium salt ofalkyloxyisoeugenol, removing the insoluble cal ciumsaltofalkyloxyisochavibetol, and treat- ,ingthe separated calcium saltswithan-acidicf- 'body torecover-the alkyloxyisochavibetol. r

and alkyloxyisoeugenol' ina substantially 3 pure state. l

A process for producing orobtaining lQl isoeugenol, characterized v byconverting. a mixture of methoxyisochavibetol and Y met-hox-yisoeugenolinto the calcium salts of the iso-' mers, by treatment with calciumoxide 01 calcium hydroxide, treating the calcium "salts with alcohol'andremoving the insoluble cal.- cium salt of alkyloxyiscchavibetol, andthereafter treating the separated calcium 'saltS With an acidic. body torecover the alkyloxyisochavibetol and alkyloxyisoeugenol in asubstantially pure state. y v 1 v THOMAS S; CARSWELL.

